One purpose of this research is to facilitate the detection, mapping and ultimate identification of genes that cause diseases in man. A second purpose is to develop methods to combine information from multiple genetic markers and environmental variables to provide accurate risk estimates for disease. For the first purpose, statistical methods of family and pedigree analysis will be further developed and implemented in computer programs. Methods of segregation, linkage and association analysis will be extended in various directions, as determined by the needs of geneticists, epidemiologists and clinicians. Segregation linkage and association ("candidate gene") analysis will all be considered together, reflecting the current needs of genetic epidemiology and current capabilities of molecular and computer technology. For the second purpose, statistical methods will be developed, relevant for the post-genomic era, for best predicting complex disease categories. Theoretical developments will continue to include studies of validity, power and robustness of all procedures developed, and special attention will be given to how studies can be most efficiently designed to unravel the genetic determinants of multifactorial diseases. The most efficient designs will necessitate sampling families and unrelated persons in special ways, and hence require the development of new methodology to extract the maximum amount of information from these specially ascertained persons and families. There will be ongoing collaborations, comprising the analysis of case-control, family and pedigree data collected by others, to ensure that the theoretical developments are relevant to current problems in the genetic analysis of multifactorial traits and to increased use of genetic markers for personalized medicine. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: This is a continuation of research that was started in[unreadable] 1969, with the aim of understanding the genetics of multifactorial traits. The next five years will put more emphasis on using the knowledge gained for health care.